Expression vectors have been used for decades as vehicles for the expression of genes or cDNAs encoding polypeptides or proteins of interest in host cells. With such vectors, viral or cellular promoters are typically used to express a gene of interest in selected host cells. For example, by using tissue specific promoters, one can selectively turn on genes in specific cell lineages, a important goal in gene therapy. For example, strategies can use a cell specific promoter to activate a suicide gene only in the targeted tumor cells.
U.S. Pat. No. 7,592,320 discloses a cancer gene therapy based on translational control of a suicide gene that does not require specific knowledge of the cancer cells, but instead targets a general characteristic that distinguishes cancer cells from normal cells, i.e., elevated eIF4E expression. The expression of a toxin or conditional toxin such as HTK is translationally repressed in normal cells by placing a complex 5′ UTR in front of its reading frame. In prototype experiments, this HTK mRNA, a transcriptional product of the BK-viralTK vector, was translationally regulated so as to largely inhibit its production in normal murine and human cells, while cancer cells efficiently translated the protein, resulting in increased sensitivity to ganciclovir (GCV). Synthesis of the HTK protein from the BK-viralTK vector containing the 5′ UTR of Fibroblast growth factor-2 (“FGF-2”) readily occurred in a panel of murine and human breast carcinoma lines, but not in normal cell lines. Subcutaneous tumors and experimental lung metastases of the breast carcinoma line MM2MT in BALB/c mice were greatly reduced by transfection with the BK-viralTK vector, followed by GCV administration. Both the BK-viralTK and the BK-TK (control) vectors were effective in reducing lung metastasis following systemic delivery of the vectors and subsequent GCV administration. However, the BK-TK vector was highly toxic to mice while little to no toxicity was seen in mice treated with the BK-viralTK vector.
U.S. Pat. No. 7,453,022 discloses a method of increasing the content of selected transgene-coded proteins or peptides in plants and includes a method of increasing the content of one or more transgene-coded proteins or peptides in a plant. The increase is an effect of a decrease in the concentration of an ATP/ADP transporter in the plant. The method depends on transformation with and expression of a cDNA encoding an ATP/ADP transporter operably linked in antisense orientation to a promoter active in the plant.
U.S. Pat. No. 7,125,902 discloses methods, compounds, and diagnostics for cancer treatment and includes methods of treating cancer employing isoxazole derivatives. Compounds and methods of using these compounds for isolating and/or detecting binding proteins, which may be indicative of a disease, are also described.
U.S. Pat. No. 6,977,244 discloses the inhibition of Bcl-2 protein expression by liposomal antisense oligodeoxynucleotides and provides compositions and methods for use in the treatment of Bcl-2-associated diseases like cancer, specifically, in the treatment of follicular lymphoma (FL). The compositions contain antisense oligonucleotides that hybridize to Bcl-2 nucleic acids, the gene products of which are known to interact with the tumorigenic protein Bcl-2. Used alone, or in conjunction with other antisense oligonucleotides, these compositions inhibit the proliferation of FL cancer cells.